Computational aspects of protein aggregation in neurodegenerative diseases

The research work performed during the doctorate focused on the computational aspects of the kinetics of aggregation and interaction of amyloidogenic proteins involved in neurological disorders. Incorrectly folded proteins may lose their colloidal stability, resulting in the formation of soluble oligomers and insoluble amyloidogenic aggregates. Amyloid fibrils are protein aggregates characterized by a filamentous β-sheet-rich structure. Although specific amyloidogenic proteins, such as α-synuclein (α-syn), β-amyloid (Aβ), huntingtin, prion protein (PrP), etc., are known to be involved in neurodegenerative diseases, the current understanding of fibril formation mechanisms implies that at certain (sometimes non-physiological) conditions almost every protein may form fibrillary structures. In the human organism, although there are few evidences of functional and physiological amyloids, these structures generally lead to amyloidosis by forming insoluble plaques, which accumulate in tissues and organs, leading to disruption of their normal functions. This doctorate thesis dealt with different problems concerning the study of neurodegenerative diseases, particularly focusing on kinetics of aggregation, new diagnostic strategies, drug discovery and drug screening methodologies